TY - JOUR
T1 - SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice
AU - Ma, Yupo
AU - Cui, Wei
AU - Yang, Jianchang
AU - Qu, Jun
AU - Di, Chunhui
AU - Amin, Hesham M.
AU - Lai, Raymond
AU - Ritz, Jerome
AU - Krause, Diane S.
AU - Chai, Li
PY - 2006/10/15
Y1 - 2006/10/15
N2 - SALL4, a human homolog to Drosophila spalt, is a novel zinc finger transcriptional factor essential for development. We cloned SALL4 and its isoforms (SALL4A and SALL4B). Through immunohistochemistry and real-time reverse-transcription-polymerase chain reaction (RT-PCR), we demonstrated that SALL4 was constitutively expressed in human primary acute myeloid leukemia (AML, n = 81), and directly tested the leukemogenic potential of constitutive expression of SALL4 in a murine model. SALL4B transgenic mice developed myelodysplastic syndrome (MDS)-like features and subsequently AML that was transplantable. Increased apoptosis associated with dysmyelopoiesis was evident in transgenic mouse marrow and colony-formation (CFU) assays. Both isoforms could bind to β-catenin and synergistically enhanced the Wnt/β-catenin signaling pathway. Our data suggest that the constitutive expression of SALL4 causes MDS/AML, most likely through the Wnt/β-catenin pathway. Our murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/β-catenin pathway's role in the pathogenesis of leukemia stem cells.
AB - SALL4, a human homolog to Drosophila spalt, is a novel zinc finger transcriptional factor essential for development. We cloned SALL4 and its isoforms (SALL4A and SALL4B). Through immunohistochemistry and real-time reverse-transcription-polymerase chain reaction (RT-PCR), we demonstrated that SALL4 was constitutively expressed in human primary acute myeloid leukemia (AML, n = 81), and directly tested the leukemogenic potential of constitutive expression of SALL4 in a murine model. SALL4B transgenic mice developed myelodysplastic syndrome (MDS)-like features and subsequently AML that was transplantable. Increased apoptosis associated with dysmyelopoiesis was evident in transgenic mouse marrow and colony-formation (CFU) assays. Both isoforms could bind to β-catenin and synergistically enhanced the Wnt/β-catenin signaling pathway. Our data suggest that the constitutive expression of SALL4 causes MDS/AML, most likely through the Wnt/β-catenin pathway. Our murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/β-catenin pathway's role in the pathogenesis of leukemia stem cells.
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U2 - 10.1182/blood-2006-02-001594
DO - 10.1182/blood-2006-02-001594
M3 - Article
C2 - 16763212
AN - SCOPUS:33749185394
SN - 0006-4971
VL - 108
SP - 2726
EP - 2735
JO - Blood
JF - Blood
IS - 8
ER -